Lambert-Eaton syndrome
Introduction
Introduction to Lambert-Eaton Syndrome Lambert-Eatonsyndrome, also known as myasthenia gravis syndrome, is a special type of myasthenia and autoimmune disease involving cholinergic synapses. First described by Lambert, Eaton, and Rooke (1956), the disease is characterized by weakness and fatigue of the proximal muscles of the limbs. The muscles of the muscles after the short-term contraction of the muscles are strengthened, and the skeletal fatigue is continued after the contraction. Lambert-Eaton syndrome is a neurotransmitter-transmitting disorder that causes presynaptic calcium channels by anti-P/Q-type voltage-gate-controlled calcium channel (P/Q-typeVGCC) antibodies. Loss causes a decrease in the number of minimal release units of acetylcholine released in the presynaptic membrane and causes muscle weakness. basic knowledge The proportion of illness: 0.001% Susceptible people: no special people Mode of infection: non-infectious Complications: impotence, orthostatic hypotension
Cause
The cause of Lambert-Eaton syndrome
Self-factor (85%):
Lambert-Eaton syndrome is a special type of myasthenia gravis and an autoimmune disease involving cholinergic synapses. The patient has an antigenic determinant IgG autoantibody associated with Ach release from the presynaptic membrane of NMJ. The antibody acts directly on the peripheral nerve. The peripheral presynaptic membrane Ach release site, as well as voltage-gated calcium channels, block calcium ion transmission, resulting in NMJ transmission disorders, speculating that the autoantigen may be a voltage-gated Ca2 channel complex section.
Pathogenesis
The autoimmune response of cancerous Lambert-Eaton syndrome patients is mainly directed to tumor cell antigenic determinants, which are cross-immunized with certain antigenic determinants of the presynaptic membrane, when immunocompetent cells encounter cancer cells with specific HLA antigens. In the case of related antigenic determinants, the immune response is initiated by a molecular mimicking mechanism. The cell line obtained from lung cancer shows that the calcium channel protein has an activated antigen, and it is speculated that the corresponding antibody exists in the tumor cell, and the patient IgG is injected into the mouse, and the Ach release is reduced, and the Amicro Structural observation revealed a functional disorder in the Ach release region.
The autoimmune mechanism of non-cancerous Lambert-Eaton syndrome is unclear. The incidence of HLA-B8 in this syndrome patients (62%) is significantly higher than that in the control group (19%), and the non-cancerous myasthenia gravis syndrome group (73%). Higher than the cancerous myasthenia gravis syndrome group (50%), Lennon et al investigated 64 patients with non-cancerous myasthenia gravis syndrome, and found that 45% of patients had one or more organs (such as thyroid, stomach or skeletal muscle). ) specific autoantibodies.
Pathological changes: The patient's muscle biopsy showed a slight increase in target fibers, atrophy of non-specific type II muscle fibers, no grouping of atrophic muscle fibers, electron microscopy showed increased post-synaptic membrane folds and secondary synaptic cleft space, Ach vesicles and The number of receptors was normal, and the nerve endings were not degenerated. Quantitative freeze-etching electron microscopy showed that the Ach release area of the patient was reduced, the unit area of the presynaptic membrane and the area of the Ach release site were reduced, and the array was abnormal. Increased number of large particle clusters provides a morphological basis for the reduction in the release of minimal Ach release units in this syndrome.
Prevention
Lambert-Eaton Syndrome Prevention
There is no effective preventive measure for this disease. Early detection and early diagnosis are the key to the prevention and treatment of this disease. Finding potential tumors such as lung cancer, treatment of primary tumors can improve neurological symptoms, if not found should be reviewed regularly.
Complication
Lambert-Eaton syndrome complications Complications, impotence, orthostatic hypotension
Cancerous myasthenia gravis syndrome and non-cancerous myasthenia gravis syndrome may involve many tissues and organs in the body, and may have clinical manifestations related to tumors and immune diseases, such as pulmonary symptoms and signs, arthritis, Rash, endocrine dysfunction, dry mouth, sphincter disorders, impotence, orthostatic hypotension, and occasional adrenal-nerve dysfunction.
Symptom
Lambert-Eaton Syndrome Symptoms Common symptoms Fatigue swing gait Reflex disappear muscle pain Swallowing difficulty Celiac disease Upper extremity Powerless alopecia areata Consonant constipation Constipation
1. Almost always adulthood, the ratio of male to female is 5:1. It is reported that the youngest one is a 9-year-old girl. No tumor is found. It usually has subacute onset, and the progression of the disease can be different. It is often found several months before the tumor. Muscle weakness and fatigue are caused in a few years. The muscle distribution is different from myasthenia gravis (MG). The skeletal muscles of the extremities are mainly composed of the skeletal muscles of the extremities, the trunk muscles, the pelvic girdle and the lower extremity muscles, and the scapula slings are particularly obvious. The lower limbs are more important than the upper limbs. The proximal end is heavier than the distal end, showing a duck step or a swaying gait, often accompanied by a weakening or disappearance of the quadriplegia. The tendon reflex can be temporarily restored after a short-term vigorous contraction of the corresponding muscle, and a cancerous polyneuropathy (carcinomatous polyneuropathy) may appear. The sputum reflex disappears, and the tumor can cause other nervous system manifestations, such as polymyositis, dermatomyositis, multifocal leukoencephalopathy and cerebellar degeneration. Some patients complain of myalgia, with obvious muscles of the thigh and no muscle bundles.
2. The first symptoms often stand up, upstairs and walking difficulties, shoulder muscles are late, and the inner nerves of the brain, such as extraocular muscles and throat muscles, may have ptosis, diplopia, dysarthria and difficulty swallowing. Less common and less affected, about 62% of patients with onset of lower extremity weakness, about 18% have myalgia or stiffness, respiratory muscle weakness requires artificial respiration, uncommon, symptoms progressively worse, patients can be forced to rub their feet Similar to MG muscle weakness, but the muscle strength can be temporarily enhanced in the first few contractions, can also check the grip strength and iliopsoas muscle strength proof, may have paresthesia, arthritis-like pain, about half of patients with autonomic symptoms The most common salivary secretion reduction caused by dry mouth, impotence, constipation, dysuria, decreased secretion of tears and sweat, orthostatic hypotension, abnormal pupillary reflex, etc., the order of symptoms usually is lower limb weakness, autonomic nervous system, upper limb weakness, cranial nerve Dominate muscle weakness, muscle pain and stiffness.
3. Clinical manifestations of cancerous and non-cancerous Lambert-Eaton syndrome
(1) Cancer-like Lambert-Eaton syndrome: male patients are mostly, about 2/3 patients with cancer, about 60% patients with small cell lung cancer, also seen in breast cancer, prostate cancer, stomach cancer, kidney cancer, rectal cancer , lymphoma, acute leukemia, reticulocyte sarcoma, etc., combined with thymoma; more than 60 to 70 years old, rarely 40 years before the onset, typical acute progressive disease, muscle weakness often occurs before the discovery of malignant tumors From month to year, patients often die from the tumor itself within a few months to several years; the disease can be seen in children, usually not related to tumors.
(2) Non-cancerous Lambert-Eaton syndrome: Another 1/3 of patients have no tumors, and many other autoimmune diseases such as pernicious anemia, hypothyroidism, hyperthyroidism, and dry (sjögren) syndrome. Rheumatoid arthritis, systemic lupus erythematosus, alopecia areata, celiac disease, psoriasis, ulcerative colitis, juvenile diabetes and myasthenia gravis, as well as reports of subacute cerebellar degeneration.
Examine
Lambert-Eaton syndrome check
1. The Tenglongxi test, the neostigmine test is sometimes positive, but far less sensitive than patients with myasthenia gravis (MG).
2. The level of serum acetylcholine receptor antibody (AchR-Ab) in patients with this disease is not increased, and some may be associated with ptosis and AchR-Ab positive. About 34% of patients with myasthenia gravis have organ-specific antibodies and immunoglobulins. Abnormal (such as IgGK accessory protein).
3. Serum muscle calcium.
4. The measurement of 125I-conotoxin labeled voltage-gated calcium channel antibody has practical value. The positive rate of P/Q calcium channel-binding antibody serological test is about 95%, and myasthenia gravis (MG) 5%. Helps identify.
5. Neurophysiological examination
(1) Low-frequency (<10Hz) repeated electrical stimulation amplitude changes little, muscle complex action potential can be reduced; high-frequency (20 ~ 50Hz) repeated electrical stimulation, muscles produce strong voluntary contraction (lasting 15s or longer), action potential amplitude Significantly increased (incremental response), increased by 2 to 20 times (more than 200% increase is positive), nerve repeated electrical stimulation is exactly opposite to myasthenia gravis (MG), which promotes calcium ions into nerve endings to promote Ach unit release Caused.
(2) After vigorously contracting for 15 s, if the amplitude is increased by more than 25%, the disease should be highly suspected. More than 100% can be diagnosed. The needle EMG can see a small multi-phase motor unit potential increase and amplitude variation, and a single muscle induces a composite action potential amplitude. Significantly reduced, single fiber EMG showed an increase in twitch such as MG.
(3) There is no abnormality in the peripheral nerves of Lambert-Eaton syndrome. A single nerve stimulation can produce a low-amplitude muscle action potential, and patients with myasthenia gravis (MG) are normal or near normal.
6. HLA-B8 and -DR3 haplotypes increase in patients with this disease, similar to other autoimmune diseases.
7. The muscle biopsy of this disease, as seen by myasthenia gravis (MG), is a normal or slight non-specific change.
Diagnosis
Diagnosis and differentiation of Lambert-Eaton syndrome
diagnosis
According to the middle-aged and elderly male lung cancer patients with proximal limb symmetry muscle weakness or fatigue, combined with dry mouth, sphincter dysfunction, myalgia and tendon reflex, weakened muscle strength after muscle contraction, sustained fatigue after systolic fatigue, The Tenglongxi test is not sensitive, the serum AchR-Ab is negative, the electromyogram high frequency nerve repeated electrical stimulation is a specific reaction, the anticholinesterase drug is not sensitive, and the Lambert-Eaton syndrome can usually be diagnosed.
Differential diagnosis
The disease should be clinically distinguished from MG.
Occasionally, patients with Lambert-Eaton syndrome have elevated serum AchR-Ab, suggesting that MG may be combined. Patients with polymyositis and snoring paralysis can be well accomplished with continuous voluntary contraction and should be identified. Arthritis patients are hindered from movement when they start exercising, and can be alleviated after continuous activities. It should be differentiated from other subacute progressive neuromuscular diseases that express muscle weakness, such as Guillain-Barré syndrome, lumbosacral plexus disease and multiple radiculopathy, all of which are demyelinating or axonal neuropathy. The electromyogram of the polar electromyogram has a discriminative value.
